氨溴索脂质体的制备及理化性质研究

Preparation and characterization of Ambroxol liposomes

目的制备氨溴索脂质体并考察其理化性质。方法采用硫酸铵梯度法制备氨溴索脂质体,在单因素考察基础上,采用正交试验设计优化脂质体的最佳处方和工艺;用透射电镜观察脂质体的外观形态,激光散射测定ξ电位和粒度分布,UV法测定脂质体的包封率,动态膜透析法探讨氨溴索脂质体体外释药特性。结果药物孵化时的形式、孵化温度、孵化时间是影响氨溴索脂质体包封率的主要的工艺因素,正交试验设计优化的最佳处方为磷脂与胆固醇之比8∶1、药脂比为1∶8、硫酸铵浓度为0.2 mol/L,最佳处方制备的脂质体为封闭的多层囊状或多层圆球体,大小均匀,平均粒径为7.189μm,ξ电位为+10.13 mv,包封率为80%,体外释放符合双向动力学方程(rα=0.998 1和rβ=0.992 3)。结论采用硫酸铵梯度法制备的氨溴索脂质体,包封率较高,体外释药有明显的缓释效果。

Purpose To study the preparation of Ambroxol liposomes and its physico-chemical property. Methods The liposomes were prepared by Ammonium Sulfate Gradient Method. Based on Single factor test, the optimum formulations and the preparation technology were optimized by orthogonal experiment. The morphology of the liposomes was detected by transmission electron microscope. The Zeta potential and particle size distribution were evaluated by laser scatter. The entrapment efficiency was determined by UV. The release character of Ambroxol liposome was studied by dynamic dialysis method. Results Factors such as the forms of Ambroxol in incubation, the temperature and time of incubation played important roles in encapsulation efficiency. The optimal formulation was obtained by an orthogonal design ： the ratio of phosphatides and cholesterol was 8 ： 1, the ratio of drug and lipids was 1 ： 8, the concentration of ammonium sulfate was O. 2 mol/L. The liposomes were muhilayer spherical or ellipsoidal in shape, with uniform size. The mean diameter and Zeta potential of Ambroxol liposomes was 7. 189 μm, and ＋ 10.13 mv, respectively. The entrapment efficiency of Ambroxol liposomes was higher than 80 %. Its process of release in vitro conformed to Bioexponential kinetics （rα = 0.998 1 and rβ = 0.992 3）. Conclusion Ambroxol could be encapsulated in liposomes at a higher encapsulation efficiency using the Ammonium Sulfate Gradient Method, and Ambroxol liposome had a good delayed-release property in vitro.